When Dr. Carlo Paribello's first two sons were diagnosed with a condition known as Fragile X Syndrome, he says it was as if there had been a death pronounced in the family.

When Dr. Carlo Paribello's first two sons were diagnosed with a condition known as Fragile X Syndrome, he says it was as if there had been a death pronounced in the family.

Now in their teens, Nicholas and Benjamin Paribello are very much loved and alive, though they display many of the mental handicaps and autistic-like behaviours that mark the chromosomal ailment.

But thanks to research at the University of Toronto, there is new hope effective treatments for the most common form of inherited mental impairment in Canada may be in the offing.

In a study to be published today in the journal Neuron, U of T physiologist Min Zhuo says it may be possible to compensate for the key brain protein missing in Fragile X patients and reverse many of the symptoms they typically suffer.

"It shows that we can actually modify," adds Paribello, founder of the Fragile X Research Foundation of Canada. "Something that you thought was not curable, and not treatable, you (may be able to) actually change."

Zhuo says the research is the first to show the specific relationship between the disease and the key neurotransmitter dopamine. The discovery, he says, will almost certainly encourage clinical trials into drugs that could modify the disease's often debilitating symptoms.

These include hyperactivity, social-skills impairment, attention deficits, hyperactivity and an autism-like withdrawal.

"It will certainly encourage lots of researchers ... to use dopamine drugs in clinical trials," says Zhuo, who holds a Canada research chair in physiology at the school.

"This is an important piece of the pathway," says Paribello, whose experience with his sons' ailments led him to found the Brampton-based foundation. "It's not all of it, but it's a big chunk of it."

The disease affects about one in 2,000 males and one in 4,000 females, says Paribello, whose sons were 3 and 18 months when diagnosed. (Paribello's two youngest sons do not have the disease.)

He says, "You think, `Oh my God, mentally (challenged), sheltered work environment for the rest of their lives. Are they going to get married? Can they go to school? Can they take care of themselves?'

"All those images you have of your hopes and aspirations, they're gone. It's like a death."

The disease is caused by a mutation to the so-called FMR1 (Fragile X Mental Retardation 1) gene, located on the X chromosome. The mutation reduces or eliminates production of the gene's normal product, a protein known as FMRP. The protein plays a critical role in allowing dopamine to perform important developmental functions.

In particular, Zhuo says, by binding to key neurons in the forebrain, dopamine can activate the proper development of learning, memory storage, attention, decision-making capacity and motor functions.

In the absence of the FMRP protein, however, dopamine is unable to trigger these normal neural activities and the growth of these functions is severely impaired.

"Deletion of this protein is what caused the problem," he says. "Dopamine is still being released in patients, dopamine still binds to the receptor, but nothing is going on after that."

Using a mouse model that lacked the FMRP protein, Zhuo's team created a rodent version of Fragile X disease.

And by promoting – through various existing drugs – the production of natural neural proteins that play a role similar to FMRP, Zhuo says his team was able to rescue the developmental processes in the afflicted mice. These, he says, quickly regained many of the same cognitive and neurological functions of their normal peers.

Because dopamine is one of the most important neurotransmitters, controlling myriad cognitive, emotional and movement functions, there are many drugs already in human use that might improve its uptake in Fragile X patients, Zhuo says.

"It's possible we may find new indications for old drugs that we never looked at before and that we never thought would work (on Fragile X)," Paribello adds.

More on thestar.com

We value respectful and thoughtful discussion. Readers are encouraged to flag comments that fail to meet the standards outlined in our
Community Code of Conduct.
For further information, including our legal guidelines, please see our full website
Terms and Conditions.